HIF‐1α‐regulated stanniocalcin‐1 mediates gemcitabine resistance in pancreatic ductal adenocarcinoma via PI3K/AKT signaling pathway
HIF‐1α‐regulated stanniocalcin‐1 mediates gemcitabine resistance in pancreatic ductal adenocarcinoma via PI3K/AKT signaling pathway
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DOI：
10.1002/mc.23420
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发表时间：
2022-07
影响因子：
4.6
通讯作者：
F. Zhao;Gang Yang;J. Qiu;Yueze Liu;Jinxin Tao;Guangyu Chen;D-X Su;L. You;Lianfang Zheng;Taiping Zhang;Yupei Zhao
中科院分区：
文献类型：
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作者：
F. Zhao;Gang Yang;J. Qiu;Yueze Liu;Jinxin Tao;Guangyu Chen;D-X Su;L. You;Lianfang Zheng;Taiping Zhang;Yupei Zhao
胰腺导管腺癌（PDAC）对一线化疗药物吉西他滨的反应较差。我们之前发现stanniocalcin‐1是一种吉西他滨耐药相关基因，但其在胰腺癌中的具体作用和功能尚不清楚。RT‐qPCR和Western blot检测差异蛋白和mRNA的表达。通过增殖和耐药实验确定基因的生物学功能。裸鼠皮下肿瘤发生实验。预后分析使用公共数据库和我们的临床数据。我们发现HIF‐1α‐调节STC1表达介导胰腺癌的化疗耐药。我们进一步探索了STC1的作用机制，确定了PI3K/AKT为STC1的下游信号通路。此外，我们分析了临床数据，发现STC1表达与吉西他滨治疗患者术后预后相关。总之，我们证明HIF‐1α/STC1/PI3K‐AKT轴参与了PDAC的进展和化疗耐药，STC1可能是PDAC治疗的潜在预后因素和治疗靶点。
Pancreatic ductal adenocarcinoma (PDAC) has a poor response to the first‐line chemotherapy drug gemcitabine. We previously identified stanniocalcin‐1 as a gemcitabine‐resistant‐related gene, but its specific role and function in pancreatic cancer remain unclear. RT‐qPCR and Western blot were used to evaluate differential protein and mRNA expressions. The biological functions of genes were determined using proliferation and drug‐resistance experiments. Subcutaneous tumorigenesis experiment was performed on nude mice. Prognostic analysis was performed using public databases and our clinical data. We found HIF‐1α‐regulated STC1 expression mediated chemoresistance in pancreatic cancer. Deeper, we explored the action mechanism of STC1 and identified PI3K/AKT as the downstream signaling pathway of STC1. Furthermore, we analyzed clinical data and found that STC1 expression was related to the prognosis of gemcitabine‐treated patients after surgery. In general, we proved the HIF‐1α/STC1/PI3K‐AKT axis participated in PDAC progression and chemoresistance, and STC1 may serve as a potential prognostic factor and therapeutic target for PDAC treatment.